Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter.
The enterohepatic circulation of bile acids is maintained by Na(+)-dependent transport mechanisms. To better understand these processes, a full-length human ileal Na(+)-bile acid cotransporter cDNA was identified using rapid amplification of cDNA ends and genomic cloning techniques. Using Northern blot analysis to determine its tissue expression, we readily detected the ileal Na(+)-bile acid cotransporter mRNA in terminal ileum and kidney. Direct cloning and mapping of the transcriptional start sites confirmed that the kidney cDNA was identical to the ileal Na(+)-bile acid cotransporter. In transiently transfected COS cells, ileal Na(+)-bile acid cotransporter-mediated taurocholate uptake was strictly Na+ dependent and chloride independent. Analysis of the substrate specificity in transfected COS or CHO cells showed that both conjugated and unconjugated bile acids are efficiently transported. When the inhibition constants for other potential substrates such as estrone-3-sulfate were determined, the ileal Na(+)-bile acid cotransporter exhibited a narrower substrate specificity than the related liver Na(+)-bile acid cotransporter. Whereas the multispecific liver Na(+)-bile acid cotransporter may participate in hepatic clearance of organic anion metabolites and xenobiotics, the ileal and renal Na(+)-bile acid cotransporter retains a narrow specificity for reclamation of bile acids.
Craddock
A L
AL
Department of Internal Medicine, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157, USA.
Love
M W
MW
Daniel
R W
RW
Kirby
L C
LC
Walters
H C
HC
Wong
M H
MH
Dawson
P A
PA
D000595:Amino Acid Sequence; D000818:Animals; D000838:Anions / Q000494:pharmacology; D001483:Base Sequence; D001647:Bile Acids and Salts / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D016466:CHO Cells; D019556:COS Cells; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D002414:Cations, Monovalent / Q000378:metabolism / Q000494:pharmacology; D003001:Cloning, Molecular; D006224:Cricetinae; D018076:DNA, Complementary; D006801:Humans; D007082:Ileum / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D027981:Symporters; D013656:Taurocholic Acid / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D000838:Anions; D001647:Bile Acids and Salts; D002352:Carrier Proteins; D002414:Cations, Monovalent; D018076:DNA, Complementary; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger; D011994:Recombinant Proteins; D027981:Symporters; C071908:sodium-bile acid cotransporter; D013656:Taurocholic Acid; D012964:Sodium